1. Field of the Invention
This invention relates to treating fungal diseases. More particularly, this invention relates to the systemic treatment of fungal diseases by oral administration of an antifungal agent selected from tolciclate and tolnaftate and to medicaments containing said agents for oral administration.
2. Description of the Prior Art
The human body is subject to many fungal infections, some of which have been a problem to man since before recorded history. Modern science has been successful in treating many fungal diseases. The most success has occurred in the topical treatment on exposed areas of the body. Numerous compounds are known to be effective in such topical treatment. However, not all fungal infections occur in exposed areas and are thus not amenable to topical treatment. Some fungal diseases occur internally or deep in the dermal layer of the skin or in unexposed areas, such as under fingernails, and can only be treated systemically. Unfortunately, only a few antifungal agents are known to be systemically effective when administered orally. One of the most widely prescribed drugs for the systemic treatment of fungal diseases is griseofulvin. Since the chronic feeding of this drug to mice results in their developing liver tumors, its use is not justified in minor or trivial infections. Accordingly, there is great interest in finding antifungal agents which can be effectively and safely administered orally.
Tolciclate and tolnaftate are known antifungal agents effective in topical treatment of fungal diseases. Tolciclate, i.e., O-(1,4-methano-1,2,3,4-tetrahydro-6-naphthyl)N-methyl-N-(m-tolyl)-thiocarb amate having the formula ##STR1## is described in U.S. Pat. No. 3,855,263. The patent indicates that the compound has antifungal activity when applied topically. Tolnaftate, i.e., methyl-(3-methylphenyl)carbamothioic acid O-2-naphthalenyl ester having the formula ##STR2## is described in U.S. Pat. No. 3,334,126. This patent indicates that tolnaftate has antifungal activity when applied topically. All indications have been that tolciclate and tolnaftate are only effective in topical treatment of fungal disease. In fact, T. Noguchi et al, in an article entitled "Antitrichophyton Activity of Naphthiomates", on pages 259-267 of Antimicrobial Agents and Chemotherapy (1962), states (page 265) that tolnaftate was found to be "totally ineffective by oral and parenteral administration" against fungal disease and "only griseofulvin was effective". In a subsequent article entitled "Antifungal Properties of Tolnaftate In Vitro and In Vivo", by M. J. Weinstein et al, on pages 595-601 of Antimicrobial Agents and Chemotherapy (1965), the following statement appears, "Tolnaftate was found to be active only by topical application and inactive by the oral and intraperitoneal routes of administration" (bottom of page 597 to top of page 598).